Microglial AKAP8L: a key mediator in diabetes-associated cognitive impairment via autophagy inhibition and neuroinflammation triggering.

BACKGROUND: Diabetes-associated cognitive impairment (DACI) poses a significant challenge to the self-management of diabetes, markedly elevating the risk of adverse complications. A burgeoning body of evidence implicates microglia as a central player in the pathogenesis of DACI. METHODS: We utilized proteomics to identify potential biomarkers in high glucose (HG)-treated microglia, followed by gene knockdown techniques for mechanistic validation in vitro and in vivo. RESULTS: Our proteomic analysis identified a significant upregulation of AKAP8L in HG-treated microglia, with concurrent dysregulation of autophagy and inflammation markers, making AKAP8L a novel biomarker of interest. Notably, the accumulation of AKAP8L was specific to HG-treated microglia, with no observed changes in co-cultured astrocytes or neurons, a pattern that was mirrored in streptozotocin (STZ)-induced diabetic mice. Further studies through co-immunoprecipitation and proximity ligation assay indicated that the elevated AKAP8L in HG-treated microglial cells interacts with the mTORC1. In the STZ mouse model, we demonstrated that both AKAP8L knockdown and rapamycin treatment significantly enhanced cognitive function, as evidenced by improved performance in the Morris water maze, and reduced microglial activation. Moreover, these interventions effectively suppressed mTORC1 signaling, normalized autophagic flux, mitigated neuroinflammation, and decreased pyroptosis. CONCLUSIONS: Our findings highlight the critical role of AKAP8L in the development of DACI. By interacting with mTORC1, AKAP8L appears to obstruct autophagic processes and initiate a cascade of neuroinflammatory responses. The identification of AKAP8L as a key mediator in DACI opens up new avenues for potential therapeutic interventions.

Prospective Investigation of Optical Genome Mapping for Prenatal Genetic Diagnosis.

BACKGROUND: Optical genome mapping (OGM) is a novel assay for detecting structural variants (SVs) and has been retrospectively evaluated for its performance. However, its prospective evaluation in prenatal diagnosis remains unreported. This study aimed to prospectively assess the technical concordance of OGM with standard of care (SOC) testing in prenatal diagnosis. METHODS: A prospective cohort of 204 pregnant women was enrolled in this study. Amniotic fluid samples from these women were subjected to OGM and SOC testing, which included chromosomal microarray analysis (CMA) and karyotyping (KT) in parallel. The diagnostic yield of OGM was evaluated, and the technical concordance between OGM and SOC testing was assessed. RESULTS: OGM successfully analyzed 204 cultured amniocyte samples, even with a cell count as low as 0.24 million. In total, 60 reportable SVs were identified through combined OGM and SOC testing, with 22 SVs detected by all 3 techniques. The diagnostic yield for OGM, CMA, and KT was 25% (51/204), 22.06% (45/204), and 18.14% (37/204), respectively. The highest diagnostic yield (29.41%, 60/204) was achieved when OGM and KT were used together. OGM demonstrated a concordance of 95.56% with CMA and 75.68% with KT in this cohort study. CONCLUSIONS: Our findings suggest that OGM can be effectively applied in prenatal diagnosis using cultured amniocytes and exhibits high concordance with SOC testing. The combined use of OGM and KT appears to yield the most promising diagnostic outcomes.

Magnetically controlled quantum thermal devices via three nearest-neighbor coupled spin-1/2 systems.

A quantum thermal device based on three nearest-neighbor coupled spin-1/2 systems controlled by the magnetic field is proposed. We systematically study the steady-state thermal behaviors of the system. When the two terminals of our system are in contact with two thermal reservoirs, respectively, the system behaves as a perfect thermal modulator that can manipulate heat current from zero to specific values by adjusting magnetic-field direction over different parameter ranges, since the longitudinal magnetic field can completely block the heat transport. Significantly, the modulator can also be achieved when a third thermal reservoir perturbs the middle spin. We also find that the transverse field can induce the system to separate into two subspaces in which neither steady-state heat current vanishes, thus providing an extra level of control over the heat current through the manipulation of the initial state. In addition, the performance of this device as a transistor can be enhanced by controlling the magnetic field, achieving versatile amplification behaviors, in particular substantial amplification factors.

Quantum heat valve and diode of strongly coupled defects in amorphous material.

The mechanical strain can control the frequency of two-level atoms in amorphous material. In this work, we would like to employ two coupled two-level atoms to manipulate the magnitude and direction of heat transport by controlling mechanical strain to realize the function of a thermal switch and valve. It is found that a high-performance heat diode can be realized in the wide piezo voltage range at different temperatures. We also discuss the dependence of the rectification factor on temperatures and couplings of heat reservoirs. We find that the higher temperature differences correspond to the larger rectification effect. The asymmetry system-reservoir coupling strength can enhance the magnitude of heat transfer, and the impact of asymmetric and symmetric coupling strength on the performance of the heat diode is complementary. It may provide an efficient way to modulate and control heat transport's magnitude and flow preference. This work may give insight into designing and tuning quantum heat machines.

Quantum squeezing-induced quantum entanglement and EPR steering in a coupled optomechanical system.

We propose a theoretical project in which quantum squeezing induces quantum entanglement and Einstein-Podolsky-Rosen steering in a coupled whispering-gallery-mode optomechanical system. Through pumping the χ(2)-nonlinear resonator with the phase matching condition, the generated squeezed resonator mode and the mechanical mode of the optomechanical resonator can generate strong quantum entanglement and EPR steering, where the squeezing of the nonlinear resonator plays the vital role. The transitions from zero entanglement to strong entanglement and one-way steering to two-way steering can be realized by adjusting the system parameters appropriately. The photon-photon entanglement and steering between the two resonators can also be obtained by deducing the amplitude of the driving laser. Our project does not need an extraordinarily squeezed field, and it is convenient to manipulate and provides a novel and flexible avenue for diverse applications in quantum technology dependent on both optomechanical and photon-photon entanglement and steering.

Methylglyoxal accumulation contributes to accelerated brain aging in spontaneously hypertensive rats.

While it is well-acknowledged that neurovascular dysfunction in hypertension is tightly associated with accelerated brain aging, we contend that the deleterious effects of hypertension may extend beyond affecting only the arteries. Methylglyoxal (MG) derived from glycolysis, is involved in the accumulation of advanced glycated end products (AGEs), which are the hallmarks of neurodegenerative disorders. Therefore, the present study aims to firstly investigate the role of MG metabolism in the hypertension-accelerated brain aging process. The results of our study indicate that the levels of MG increase with age in both the plasma and hippocampus of SHRs at 12, 16, and 30 weeks old. AGE methylglyoxal-hydro imidazoline-1 (MG-H1) is primarily localized in astrocytes, while its presence was not observed in neurons and microglia within the hypertensive hippocampus. Our observations also suggest that angiotensin II (Ang II) enhances glucose uptake and glycolysis while reducing the expression of Glo1 in cultured astrocytes. N-acetylcysteine (NAC) was found to counteract the increase in escape latency and inhibit the activation of the AGEs-RAGE axis in 30-week-old SHRs. NAC decreased Iba-1 immunofluorescence intensity, inhibited the levels of pro-inflammatory markers, and enhanced the abundance of anti-inflammatory markers in the hippocampus of SHRs. Moreover, NAC reduced the immunofluorescence signal of 4HNE and increased the content of GSH and SOD in SHRs. Finally, NAC was observed to inhibit apoptosis in the hippocampus of SHRs. Collectively, we firstly showed the enhanced accumulation of MG in the hypertensive brain, whereas the clearance of MG by NAC treatment mitigated the aging process and attenuated AGEs generation, neuroinflammation, and oxidative damage.

Photon blockade with a trapped Λ-type three-level atom in asymmetrical cavity.

We propose a scheme to manipulate strong and nonreciprocal photon blockades in asymmetrical Fabry-Perot cavity with a Λ-type three-level atom. Utilizing the mechanisms of both conventional and unconventional blockade, the strong photon blockade is achieved by the anharmonic eigenenergy spectrum brought by Λ-type atom and the destructive quantum interference effect induced by a microwave field. By optimizing the system parameters, the manipulation of strong photon blockade over a wide range of cavity detuning can be realized. Using spatial symmetry breaking introduced by the asymmetry of cavity, the direction-dependent nonreciprocal photon blockade can be achieved, and the nonreciprocity can reach the maximum at optimal cavity detuning. In particular, manipulating the occurring position of nonreciprocal photon blockade can be implemented by simply adjusting the cavity detuning. Our scheme provides feasible access for generating high-quality nonreciprocal single-photon sources.

Release of virtual photon and phonon pairs from qubit-plasmon-phonon ultrastrong coupling system.

The most important difference between ultrastrong and non-ultrastrong coupling regimes is that the ground state contains excitations. We consider a qubit-plasmon-phonon ultrastrong coupling (USC) system with a three-level atom coupled to the photon and phonon via its upper two energy levels and show that spontaneous emission of the atom from its intermediate to its ground state produces photon and phonon pairs. It is shown that the current system can produce a strong photon/phonon stream and the atom-phonon coupling plays the active role, which ensures the experimental detection. The emission spectrum and various high-order correlation functions confirm the generation of the pairs of photons and phonons. Our study has important implications for future research on virtual photon and phonon pairs creation in the ground state of the USC regime.

Quantum thermal diode dominated by pure classical correlation via three triangular-coupled qubits.

A quantum thermal diode is designed based on three pairwise coupled qubits, two connected to a common reservoir and the other to an independent reservoir. It is found that the internal couplings between qubits can enhance heat currents. If the two identical qubits uniformly couple with the common reservoir, the crossing dissipation will occur, leading to the initial-state-dependent steady state, which can be decomposed into the mixture of two particular steady states: the heat-conducting state generating maximum heat current and the heat-resisting state not transporting heat. However, the rectification factor doesn't depend on the initial state. In particular, we find that neither quantum entanglement nor quantum discord is present in the steady state, but the pure classical correlation shows a remarkably consistent behavior as the heat rectification factor, which reveals the vital role of classical correlation in the system.

Quantum heat diode versus light emission in circuit quantum electrodynamical system.

Precisely controlling heat transfer in a quantum mechanical system is particularly significant for designing quantum thermodynamical devices. With the technology of experiment advances, circuit quantum electrodynamics (circuit QED) has become a promising system due to controllable light-matter interactions as well as flexible coupling strengths. In this paper, we design a thermal diode in terms of the two-photon Rabi model of the circuit QED system. We find that the thermal diode can not only be realized in the resonant coupling but also achieve better performance, especially for the detuned qubit-photon ultrastrong coupling. We also study the photonic detection rates and their nonreciprocity, which indicate similar behaviors with the nonreciprocal heat transport. This provides the potential to understand thermal diode behavior from the quantum optical perspective and could shed new insight into the relevant research on thermodynamical devices.

Strophiofimbrins A and B: Two Rearranged Norditerpenoids with Novel Tricyclic Carbon Skeletons from Strophioblachia fimbricalyx.

Two rearranged norditerpenoids with novel tricyclic carbon skeletons, strophiofimbrin A (1) and strophiofimbrin B (2), were isolated from Strophioblachia fimbricalyx. Their structures were established by 1D/2D NMR spectroscopy, HRESIMS, quantum chemistry calculations, and X-ray diffraction analyses. 1 and 2 represented the first examples of diterpenoids with unprecedented 5/6/7-fused ring systems. In the proposed biosynthetic pathway, they were suspected to derive from cleistanthane norditerpenoids via ring opening, expansion, cyclization, and rearrangement based on the existence of phenanthrenone and cleistanthane diterpenoids from Strophioblachia and Trigonostemon, two closely related genera of the Euphorbiaceae family. Furthermore, compounds 1 and 2 exhibited significant proliferation inhibition and obvious neuroprotective effects.

[Birth weights of singleton neonates of 14 Chinese ethnic groups in 11 cities of China]. / 中国11市14ä¸ªæ°‘æ—å•èƒŽå„¿å‡ºç”Ÿä½“é‡ç ”ç©¶.

OBJECTIVES: To develop the birth weight curves of the Chinese Han (26-41 weeks of gestation) and Zhuang (28-41 weeks of gestation) singleton neonates in 11 cities of China, as well as the birth weight means of full-term neonates of 14 Chinese ethnic groups. METHODS: The live singleton neonates who were born in 11 maternal and child health care hospitals from 11 cities of China between January 2017 and December 2020 were classified according to the mother's ethnic group. Birth weight means were calculated for the full-term neonates of each ethnic group. For the Han and Zhuang singleton neonates with a large sample size, the Lambda-Mu-Sigma (LMS) method was used to establish the birth weight percentile curves of the Han and Zhuang singleton neonates with different gestational ages. RESULTS: A total of 105 365 live singleton neonates were included, among whom the Han neonates had the highest number of 84 851 (26-41 weeks of gestation), followed by the Zhuang neonates (12 803 neonates with a gestational age of 28-41 weeks). The neonates of the other Chinese ethnic groups enrolled were live full-term singleton neonates, with a sample size of more than 100 neonates for each ethnic group. The 3rd-97th percentile curves of birth weight were established for the Han singleton neonates with a gestational age of 26-41 weeks and the Zhuang singleton neonates with a gestational age of 28-41 weeks. The birth weight curves of the Han singleton neonates at each gestational age were higher than those of the Zhuang singleton neonates. Birth weight means (3 199-3 499 g) and standard deviations were determined for 14 Chinese ethnic groups, i.e., Li, Mulao, Zhuang, Yao, Dong, Miao, Han, Buyi, Mongolian, Tujia, Yi, Hui, Man, and Korean ethnic groups. The Li ethnic group had the lowest birth weight, followed by the Mulao, Zhuang, Yao, Dong, Miao, Han, Buyi, Mongolian, Tujia, Yi, Hui, Man, and Korean ethnic groups. CONCLUSIONS: The 3rd-97th percentile curves of birth weight are developed for the Han (26-41 weeks of gestation) and Zhuang (28-41 weeks of gestation) singleton neonates in 11 cities of China, and birth weight means are determined for the full-term neonates of 14 Chinese ethnic groups in 11 cities of China, which provides a reference for evaluating the intrauterine growth of neonates in these ethnic groups.

Mechanically controllable nonreciprocal transmission and perfect absorption of photons.

Photon absorption and nonreciprocal photon transmission are studied in a rotating optical resonator coupled with an atomic ensemble. It is demonstrated that the perfect photon absorption is accompanied by optical bistability when the resonator is static. If the spinning detune is adjusted to some particular values, we find that the amplified unidirectional photon transmission can be realized. We have explicitly given the perfect photon absorption conditions and the maximal adjustable amplification rate. It is found that the coupling of the resonator and the atomic ensemble is necessary for perfect photon absorption, and the phase difference of the two input fields only affects the perfect absorption point. It gives new insight into the design of photon absorbers and optical switches.

Birth weight curves of twin neonates with a gestational age of 25-40 weeks and their regional differences in 11 cities of China: an analysis of 17 256 cases. / 中国11市17 256例胎龄25~40周双胎儿出生体重曲线及地区差异特征.

OBJECTIVES: To develop the birth weight curve of twin neonates with a gestational age of 25-40 weeks, and to investigate the regional differences of the birth weight curve. METHODS: A total of 11 maternal and child health care hospitals with more than 7 000 neonates delivered annually were selected in 11 cities of China (Haikou, Guangzhou, Liuzhou, Guilin, Quanzhou, Shenzhen, Chongqing, Chengdu, Changsha, Ningbo, and Lianyungang), and all live twin neonates delivered in the 11 hospitals from January 1, 2017 to December 31, 2020 were enrolled for the development of birth weight curves. RESULTS: A total of 17 256 twin neonates with a gestational age of 25-40 weeks from the 11 cities were included in the study. The reference values of the 3rd-97th percentiles of birth weight of twin neonates for the total of the 11 cities and for each of the 11 cities in China were established, and the birth weight percentile curves were drawn. The birth weight curve level of twin neonates in Liuzhou was lower than the average level of the 11 cities; the birth weight curve level of twin neonates in Ningbo was higher than the average level of the 11 cities; the birth weight curve level of twin neonates in Lianyungang was obviously higher than the average level of the 11 cities; the birth weight curve level of twin neonates in other 8 cities was almost the same as the average level of the 11 cities. CONCLUSIONS: The reference values of the 3rd-97th percentiles of birth weight of twin neonates for the total of the 11 cities and for each of the 11 cities are developed, which can be used as a reference for evaluating the intrauterine growth of twin neonates in the region. The level of intrauterine growth of twin neonates in some cities is different from the average level of the 11 cities of China.

Effect of vision loss on plasticity of the head and neck proprioception.

AIM: To investigate whether head and neck proprioception and motor control could be compensatory enhanced by long-term vision loss or impairment. METHODS: Individuals who were blind, low vision or sighted were included in the study, which would undergo the head repositioning test (HRT). The constant error (CE), absolute error (AE), variable error (VE) and root mean square error (RMSE) of each subject were statistically analyzed. Data were analyzed using the SAS 9.4. Tukey-Kramer for one-way ANOVA was used for comparison of blind, low vision, and sighted subjects, as well as to compare subjects with balanced vision, strong vision in the left eye and strong vision in the right eye. Independent sample t-test was used to compare subjects with congenital blindness and acquired blindness, as well as left and right hand dominance subjects. RESULTS: A total of 90 individuals (25 blind subjects, 31 low vision subjects, and 34 sighted subjects) were included in the study. Among the blind subjects, 14 cases had congenital blindness and 11 cases had acquired blindness. Among the blind and low vision subjects, 21 cases had balanced binocular vision, 17 cases had strong vision in the left eye and 18 cases had strong vision in the right eye. Among all subjects, 11 cases were left hand dominance, and 79 cases were right hand dominance. There were significant differences in AE, VE, and RMSE in head rotation between blind, low vision, and sighted subjects (P<0.01), in AE, VE, and RMSE between blind and sighted (P<0.01), and in VE and RMSE between low vision and sighted (P<0.05). No significant difference between blind and low vision (P>0.05). Significant differences in CE and AE of head right rotation and CE of general head rotation between congenital and acquired (P<0.05). No significant differences between left and right hand dominance and in balance or not of binocular vision (P>0.05). CONCLUSION: Long-term vision loss or impairment does not lead to compensatory enhancement of head and neck proprioception and motor control. Acquired experience contributes to HRT performance in the blind and has long-lasting effects on plasticity in the development of proprioception and sensorimotor control.

Antidepressant-like effects of dezocine in mice: involvement of 5-HT1A and κ opioid receptors.

Dezocine is an opioid with low efficacy at µ-opioid and κ-opioid receptors. It also inhibits the reuptake of norepinephrine and serotonin. Dezocine is an effective analgesic against various clinical painful conditions and is widely used in many Asian countries. Given the unique pharmacology of dezocine, the drug may also have antidepressant-like properties. However, no published preclinical study has explored this possibility. This study examined the potential antidepressant-like activity of dezocine in mice. Male ICR mice were used in the forced swimming test, the tail suspension test, the warm water tail withdrawal test and locomotor activity test to test the effects of dezocine (0.3-3.0 mg/kg). The 5-HT1A receptor antagonist WAY-100635 (1 mg/kg), the µ-opioid receptor antagonist ß-funaltrexamine (2 mg/kg) and the κ-opioid receptor agonist U50488 (1 mg/kg) were also studied in combination with dezocine. Dezocine produced a dose-dependent decrease in the immobility time in the forced swimming test and tail suspension test at doses that did not alter the motoric activity as determined in the locomotion test. WAY-100635 and U50488 but not ß-funaltrexamine pretreatment significantly blocked the effects of dezocine. Dezocine dose-dependently increased the latency in the tail withdrawal test which was blocked by WAY-100635 and ß-funaltrexamine. Combined, these results suggest that dezocine may have antidepressant-like effects. Considering the well-documented analgesic property of dezocine, it may be useful to treat pain and depression comorbidity.

Long Non-coding RNA XIST Attenuates Diabetic Peripheral Neuropathy by Inducing Autophagy Through MicroRNA-30d-5p/sirtuin1 Axis.

Diabetic peripheral neuropathy (DPN) is a prevalent diabetes mellitus (Feldman et al., 2017) complication and the primary reason for amputation. Meanwhile, long non-coding RNAs (lncRNAs) are a type of regulatory non-coding RNAs (ncRNAs) that broadly participate in DPN development. However, the correlation of lncRNA X-inactive specific transcript (XIST) with DPN remains unclear. In this study, we were interested in the role of XIST in the modulation of DPN progression. Significantly, our data showed that the expression of XIST and sirtuin1 (SIRT1) was inhibited, and the expression of microRNA-30d-5p (miR-30d-5p) was enhanced in the trigeminal sensory neurons of the diabetic mice compared with the normal mice. The levels of LC3II and Beclin-1 were inhibited in the diabetic mice. The treatment of high glucose (HG) reduced the XIST expression in Schwann cells. The apoptosis of Schwann cells was enhanced in the HG-treated cells, but the overexpression of XIST could block the effect in the cells. Moreover, the levels of LC3II and Beclin-1 were reduced in the HG-treated Schwann cells, while the overexpression of XIST was able to reverse this effect. The HG treatment promoted the production of oxidative stress, while the XIST overexpression could attenuate this result in the Schwann cells. Mechanically, XIST was able to sponge miR-30d-5p and miR-30d-5p-targeted SIRT1 in the Schwann cells. MiR-30d-5p inhibited autophagy and promoted oxidative stress in the HG-treated Schwann cells, and SIRT1 presented a reversed effect. MiR-30d-5p mimic or SIRT1 depletion could reverse XIST overexpression-mediated apoptosis and autophagy of the Schwann cells. Thus, we concluded that XIST attenuated DPN by inducing autophagy through miR-30d-5p/SIRT1 axis. XIST and miR-30d-5p may be applied as the potential targets for DPN therapy.

Common Environmental Effects on Quantum Thermal Transistor.

Quantum thermal transistor is a microscopic thermodynamical device that can modulate and amplify heat current through two terminals by the weak heat current at the third terminal. Here we study the common environmental effects on a quantum thermal transistor made up of three strong-coupling qubits. It is shown that the functions of the thermal transistor can be maintained and the amplification rate can be modestly enhanced by the skillfully designed common environments. In particular, the presence of a dark state in the case of the completely correlated transitions can provide an additional external channel to control the heat currents without any disturbance of the amplification rate. These results show that common environmental effects can offer new insights into improving the performance of quantum thermal devices.

Comparison of robot-assisted retroperitoneal laparoscopic adrenalectomy versus retroperitoneal laparoscopic adrenalectomy for large pheochromocytoma: a single-centre retrospective study.

BACKGROUND: To evaluate the feasibility and safety of robot-assisted retroperitoneal laparoscopic adrenalectomy (RARLA) for large pheochromocytomas (PHEOs; size≥6 cm) compared with retroperitoneal laparoscopic adrenalectomy (RLA). METHODS: Fifty-one patients who underwent adrenalectomy for large PHEOs between March 2016 and January 2019 were enrolled and divided into two groups, including 32 RLA cases and 19 RARLA cases. We compared the perioperative efficacy and long-term follow-up results between the two groups. RESULTS: Preoperative data, including demographics, comorbidities and tumour characteristics, were similar between the groups. Intraoperatively, the RARLA group had a lower incidence of haemodynamic instability (26.3% vs. 56.2%, P = 0.038) and less intraoperative blood loss (100 ml vs. Two hundred milliliter, P = 0.042) than the RLA group. The groups showed no significant differences in operative time or transfusion rates. Postoperatively, the time to diet resumption, time to ambulation, time to drainage removal and postoperative hospital stay were shorter in the RARLA group than in the RLA group (1 d vs. 2 d, P = 0.027; 1 d vs. 2 d, P = 0.034; 3 d vs. 5 d, P = 0.002; 5 d vs. 6 d, P = 0.02, respectively). The groups exhibited no significant differences in the duration of anaesthetic use, complications, or long-term follow-up results for the blood pressure (BP) improvement rate. CONCLUSIONS: Compared with RLA, RARLA is a safe, feasible and even optimized procedure for large PHEOs.

Quantum speed limit based on the bound of Bures angle.

In this paper, we investigate the unified bound of quantum speed limit time in open systems based on the modified Bures angle. This bound is applied to the damped Jaynes-Cummings model and the dephasing model, and the analytical quantum speed limit time is obtained for both models. As an example, the maximum coherent qubit state with white noise is chosen as the initial states for the damped Jaynes-Cummings model. It is found that the quantum speed limit time in both the non-Markovian and the Markovian regimes can be decreased by the white noise compared with the pure state. In addition, for the dephasing model, we find that the quantum speed limit time is not only related to the coherence of initial state and non-Markovianity, but also dependent on the population of initial excited state.